Diketones enzymatic reduction

Figure 9.4 Enzymatic reduction ofa-alkyl- 1,3-diketones with NADPH-dependent KREDs...

This indeed verifies the dynamic kinetic resolution of roc-3 through enzymatic reduction, representing the first example for the dynamic kinetic resolution of an open-chain 2-alkyl-substituted 1,3-diketone through reduction under neutral conditions. 

Diols may be prepared by reduction of a-diketones or a-hydroxy ketones such as biacetyl, benzoin, and benzil. Substituted benzoins containing methoxyl and p-dimethylamino groups have been reduced catalytically over platinum oxide and by sodium amalgam and alcohol. Levorotatory propylene glycol is made from acetol, CHjCOCHjOH, by an enzymatic reduction with yeast. ... 

The selective enzymatic reduction of 2-substituted / -keto esters or /S-diketones is more interesting than that of unsubstituted compounds since two stereogenic centers can be introduced into the molecule in one step. The observation that baker s yeast reduction of these compounds results in predominantly one of the four possible diastereomeric products has been explained by a keto- enol equilibration of the enantiomeric / -dicarbonyls with the simultaneous removal of one of these substrates by an asymmetric reduction49. 

An novel method for the DKR of a 2-methyl-substituted unsymmetrical 1,3-diketone via enzymatic reduction was described by Muller s group in 2001. As shown in Scheme 3.6, the enantiopure anti product was produced in excellent diastereoselectivity and moderate yield. 

In addition, it is clear that biocatalytic reductions will form part of a synthetic sequence and therefore wider issues of integration will also need to be considered. For example, a recent publication [73] reported the enzymatic reduction of diketones in a one-pot reactor linked with a Suzuki coupling. Such chemoenzymatic approaches will open up many new opportunities for reductions in the future. Understanding how to integrate such sequences together will also be important. 

Further studies by the same research group led to the sequential enzymatic reduction of diketone 40 to the one-pot synthesis of two stereoisomers of the corresponding diols 42a and 42b, in high chemical yields followed by excellent selectivities (Scheme 12.21) [56]. 

The possibilily of obtaining (100) by the allqrlation of (359) with 1,3-dichlor0-2-butene has also been studied [449]. However, this route was abandoned, since the hydrolysis of the chlorovinyl grouping of the product obtained (375) was accompanied by its decomposition. The diketone (100), containing one asymmetric center, as resolved into its optical isomers by enzymatic reduction with Curviilaria falcata and other microorganisms [114, 116]. 

Preparation and phytochemical reduction of 2,2 -thenoin and 2,2 -thenil have been studied in the authors laboratory (20a). It has been shown that 2,2 -thenoin gives a color reaction similar to that shown by benzoin and other acyloin condensation products in- the presence of alcoholic alkali. The hydroxy ketone may be oxidized by iodine in the presence of sodium methoxide to give the diketone, 2,2 -thenil, in excellent yields. Phytochemical reduction was shown also to be applicable to both compounds. It is significant that thenoin differs from benzoin, since reduction products were not obtained enzymatically from the latter. 

Baker s yeast offers the synthetic chemist an enzymatic method for the asymmetric reduction of p-keto esters, a-hydroxyaldehydes and ketones, and p-diketones. Reviews (a) Rene Csuk, R. Glaenzer, B. 1. Chem. Rev. 1991, 91, 49-97. (b) Servi, S. Synthesis, 1990, 1-25. 

Moreover, unsaturated keto silanes and diketones obtained according to eq 1 can be easily reduced to saturated keto silanes or 1,6-dicarbonyl confounds unsaturated keto silanes can be transformed into enantiomerically enriched hydroxy derivatives by reduction and enzymatic kinetic resolution. MonosUylated unsaturated sulfides, precursors of a variety of dienylsilanes, can be also obtained by chemoselective electrophilic substitutions. ... 

---